Candida albicans is a member of the indigenous human flora and is responsible for the largest percentage of oral and vaginal infections of fungal origin in uncompromised individuals. More recently, severe candidiasis has been recognized as a consequence of medical treatments such as immunosuppression or chemotherapy; and in the AIDS patient C. albicans oro-esophageal infections are often encountered. During the past several years he has performed investigations designed to study the plasma membrane/cell wall structure and function of C. albicans, particularly as they relate to pathogenesis and morphogenesis of the organism. These investigations have evolved towards analysis of spontaneous, cerulenin-resistant mutant strains that are also relatively avirulent compared to the parental strain. In addition, it has been documented that a variety of differences exist between the strains, particularly in regard to cell wall/ membrane structure, and is long-term aim is to understand the basis and significance of these changes. Preliminary data suggest that cerulenin resistance of the mutant strains is related in part to mutation of its target, fatty acid synthase, rather than to changes in permeability, as might be reasoned from the altered cell surface structure observed. Dr. Cihlar therefore, plans to focus the proposed investigations on biochemical genetic, and molecular analysis of: i) fatty acid synthase of the strains, and ii) the genes that specify the enzyme complex. Furthermore, he will begin to approach the intriguing question of whether fatty acid synthase function may account for the phenotypic variation of the mutant strains.